This is a renewal request for a Program Project Grant which focuses on cardiac electrophysiology and cardiac contractility investigations with the long term goal of achieving a good physiological understanding of cardiac electrical and mechanical events and thereby provide useful and new diagnostic methods leading ultimately to improved therapy of patients with many types of heart disease. To this end, the work is to be done by a tightly knit group of investigators from varied disciplines including physicians, physiologists, engineers, physicists, and computer scientists. Previous work in this program has led to the development of new biophysical methods allowing detailed electrical measurements of selected cardiac structures to measuring total heart electrical activity to relating this in a mathematical form with the potentials on the body surface. With these methods our objective is to develop conceptual and mathematical models which will provide a good knowledge of the origin and perpetuation of arrhythmias and to understand the origin of body surface potentials in most abnormal cardiac states. This approach will be continued through developing appropriate mathematical models to relate intracellular to extracellular potentials, extracellular potentials to those surrounding the heart, and epicardial potentials to those on the entire body surface and to confirm all of these models by appropriate experimental measurements. The ultimate aim of the muscle mechanics studies is to obtain a complete description of the changes in cardiac contractility, to understand their origin at the sarcomere level, as well as to evaluate their manifestation in the intact heart in man. This aim will be pursued through two types of studies: those on whole muscle with respect to how length, rate, pattern of stimulation, and environmental conditions combine to determine overall contractility and those that require study of the contractile element itself to determine the basic mechanical properties of the sarcomere.